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Metastatic Colorectal CancerPhase 2BETWEENNCT07071844

BETWEEN: Biweekly Bevacizumab + Trifluridine/Tipiracil to Reduce Grade 3-4 Neutropenia in mCRC Patients

A Phase 2 study testing Trifluridine/tipiracil and Bevacizumab in people with Metastatic Colorectal Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 10 sites in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This study was design to: To assess the impact of a biweekly (experimental arm) compared to a conventional administration (control arm) on the rate of grade 3-4 neutropenia in metastatic colorectal cancer (mCRC) patients treated with trifluridine/tipiracil plus bevacizumab, and To identify predictive clinical and… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
Trifluridine/tipiracil and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
10 sitesFrance
Study dates
Sep 2025to Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and dated informed consent,
  • Patients willing and able to comply with protocol requirements,
  • Age ≥ 18 years,
  • ECOG PS 0-1,
  • Histologically proven colorectal adenocarcinoma,
  • Stage IV disease,
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  • Previous chemotherapy regimens with each of the following agents: fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF therapy (bevacizumab, aflibercept, and anti-EGFR therapy (cetuximab or panitumumab for tumors with RAS and/or BRAF wild-type),
  • Tumor assessment (CT-scan or MRI) no later than 21 days prior to treatment - at least one measurable or evaluable lesion as assessed by computed tomography (CT)-scan or magnetic resonance imaging (MRI) according to RECIST,
  • Known BRAF and RAS mutational status, and microsatellite instability/mismatch repair deficiency (MSI/dMMR) status,
  • Have life expectancy of at least 3 months,
  • Adequate hematologic function: neutrophils >1.5 x 10^9/L; platelets >100 x 10^9/L; hemoglobin ≥ 9 g/dL,
  • Adequate renal function: Calculated (regardless of the calculation method) creatinine clearance (CrCl) ≥30 mL/min), proteinuria < 2+ (dipstick urinalysis) or ≤1g / 24h,
  • Adequate liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit normal (ULN; ≤5 x ULN in case of liver metastasis), total bilirubin ≤1.5 x ULN (<2 x ULN if hyperbilirubinemia is due to Gilbert's syndrome), albumin ≥25 g/L,
  • Clinical and blood baseline evaluations no later than 14 days prior to treatment,
  • Ability to swallow oral tablets,
  • Women must be surgically sterile or postmenopausal, or not be pregnant, breastfeeding, or expecting to conceive during the study. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to starting trifluridine/tipiracil treatment. WOCBP must agree to use an adequate method of contraception or birth control for the duration of study treatment and least 6 months (trifluridine/tipiracil, bevacizumab) after the last dose of the study treatment,
  • Males who are fertile and sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and at least 6 months (trifluridine/tipiracil, bevacizumab) after the last dose of the study treatment.
  • Is willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study,
  • Registration with the French National Health Care System or PUMA (Protection Universelle Maladie).

Who cannot join

  • ECOG PS 2,
  • Medical history or evidence of CNS metastasis upon physical examination, unless adequately treated (e.g., non-irradiated CNS metastasis, seizure not controlled with standard medical therapy, patients are stable without evidence of progression for at least 28 days prior to inclusion),
  • Local or locally advanced disease (stage I to III),
  • Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, immunotherapy),
  • Unresolved grade ≥3 non-hematologic toxicity related to previous chemotherapy regimen (excluding alopecia and skin pigmentation),
  • Dihydropyrimidine dehydrogenase (DPD) deficiency (uracilemia dosage >16 ng/ml); Uracilemia dosing results must be available before inclusion,
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  • Treatment with warfarin,
  • Treatment with any other investigational medicinal product (IMP) within 28 days prior to inclusion,
  • Symptomatic carcinomatosis with occlusive symptoms or ascites requiring paracentesis,
  • Other serious and uncontrolled non-malignant disease (e.g., active infection requiring systemic therapy, coronary stenting or myocardial infarction, or stroke in the past 6 months prior inclusion),
  • Severe or uncontrolled active acute or chronic infection,
  • Major surgery within 28 days (4 weeks) prior to inclusion,
  • Gastrointestinal disease that could potentially interfere with study drug absorption,
  • Uncontrolled diabetes mellitus, hypertension, or cardiac arrhythmia,
  • Active (or history of) interstitial lung disease or pulmonary hypertension,
  • Major adverse cardiovascular event within 6 months prior to inclusion,
  • Severe/unstable angina, or NYHA class III or IV heart failure,
  • Systemic immunosuppressive therapy, except steroids given prophylactically or at chronic low dosage (≤20 mg/day prednisone equivalent),
  • Radiotherapy within 28 days (4 weeks) before randomization, except for palliation,
  • Serious nonhealing wound, ulcer or bone fracture,
  • Deep vein thromboembolic event within 28 days (4 weeks) prior to inclusion,
  • Known clinically relevant coagulopathy, bleeding diathesis or bleeding event within 28 days (4 weeks) prior to inclusion,
  • Malignant disease other than mCRC,
  • Other concomitant or previous malignancy, except i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
  • Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
  • Note: In patients who have previously received or are receiving intravenous bisphosphonates, invasive dental procedures should be avoided, if possible.
  • Note: Caution is required when using medicinal products that are human thymidine kinase substrates, e.g., zidovudine. Such medicinal products, if used concomitantly with trifluridine/tipiracil, may compete with the effector, trifluridine, for activation via thymidine kinases. Therefore, when using antiviral medicinal products that are human thymidine kinase substrates, monitor for possible decreased efficacy of the antiviral medicinal product, and consider switching to an alternative antiviral medicinal product that is not a human thymidine kinase substrate, such as lamivudine, didanosine, and abacavir.
  • Note: It is unknown whether trifluridine/tipiracil may reduce the effectiveness of hormonal contraceptives. Therefore, women using hormonal contraceptive must also use a barrier contraceptive method.
  • Human immunodeficiency virus (HIV)-infected patients or otherwise known to be HIV-positive,
  • Untreated hepatitis B virus (HBV) or hepatitis C virus (HCV),
  • Concomitant administration of prophylactic phenytoin and live attenuated virus vaccine such as yellow fever vaccine 28 days (4 weeks) prior to treatment,
  • Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness,
  • Under legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapability of giving consent.

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Marie-Line GARCIA LARNICOL, MD contact

+33 (01) 40 29 85 04

marie-line.garcia-larnicol@gercor.com.fr

10 sites in 1 country

France10 sites

  • CHU Amiens

    Amiens

    Vincent HAUTEFEUILLEI, MD

  • Centre Hospitalier Universitaire -Besançon

    Besançon

    Antoine EL KADDISSI, MD

  • Centre François Baclesse

    Caen

    Marie Pierre GALAIS, MD

  • Centre Hospitalier Departemental Vendee - Site Des Oudairies

    La Roche-sur-Yon

    Lucile BAUGUION, MD

  • Centre Hospitaler Universitaire de Lille

    Lille

    Anthony TURPIN, MD

  • Hôpital privé Jean MERMOZ

    Lyon

    Jérôme DESRAME, MD

  • CHU Saint-Antoine

    Paris

    Romain Cohen, MD

  • Institut Saint Catherine

    Paris

    Clémence TOULLEC, MD

  • CHU de BORDEAUX Hôpital HAUT-LEVEQUE

    Pessac

    Denis SMITH, MD

  • Institut de cancérologie Strasbourg Europe

    Strasbourg

    Meher BEN ABDELGHANI, MD

Other trials in France

About this study

Official title: BEvacizumab Plus Trifluridine/Tipiracil in a Bi-WEEkly Administration to Reduce Grade 3-4 Neutropenia in Patients With mCRC: A Prospective, Multicenter, Comparative, Randomized GERCOR G-124 BETWEEN Phase II Study

This study was design to:

  • To assess the impact of a biweekly (experimental arm) compared to a conventional administration (control arm) on the rate of grade 3-4 neutropenia in metastatic colorectal cancer (mCRC) patients treated with trifluridine/tipiracil plus bevacizumab, and
  • To identify predictive clinical and biological factors for grade 3-4 neutropenia in this patient population.
Read the detailed description

Trifluridine/tipiracil is effective in refractory metastatic colorectal cancer (mCRC), as shown in phase III trials, including SUNLIGHT, which demonstrated improved PFS and OS when combined with bevacizumab, setting a new third-line standard. However, this combination raises grade 3-4 neutropenia rates to 43-66%, often leading to dose reductions or delays. A biweekly regimen tested in a small phase II trial showed reduced neutropenia (15.9%) but limited generalizability. Neutropenia remains a major concern, with 9.5% mortality. G-CSF may help manage risk, especially in high-risk patients (LONGBOARD).

Being tested
Trifluridine/tipiracil, Bevacizumab
Keywords
Trifluridine/Tipiracil, metastatic colorectal cancer, neutropenia, bevacizumab
Medical subject headings
Colorectal Neoplasms, Neutropenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trifluridine/tipiracilDrug

    Also called LONSURF

    35 mg/m², orally

  • BevacizumabDrug

    Also called AVASTIN

    5 mg/kg, intravenous route

Study groups in NCT07071844
Study groupRoleWhat they receive
Arm A (experimental) - Trifluridine/tipiracil plus bevacizumab biweekly administrationExperimentalTrifluridine/tipiracil: 35 mg/m², twice daily (BId) orally, on days 1-5 and days 15-19; 1 cycle every 28 days. + Bevacizumab: 5 mg/kg intravenously (IV) on day 1 and day 15; 1 cycle every 28 days.
Receives: Drug: Trifluridine/tipiracil; Drug: Bevacizumab
Arm B (control) - Trifluridine/tipiracil plus bevacizumab conventional administrationActive comparatorTrifluridine/tipiracil: 35 mg/m² Bid orally on days 1-5 and days 8-12; 1 cycle every 28 days. + Bevacizumab: 5 mg/kg IV on day 1 and day 15; 1 cycle every 28 days.
Receives: Drug: Trifluridine/tipiracil; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The occurrence of at least one grade 3-4 neutropenia

    The occurrence of 3-4 neutropenia in mCRC patients undergoing treatment with the combination of bevacizumab and bi-weekly administration of trifluridine/tipiracil (experimental arm) compared to a conventional administration (control arm).

    Measured: From randomization up to 14 days after the end of treatment

Secondary outcomes (6)

  1. Overall survival (OS)

    OS in both arms; calculated from the date of randomization to the date of death from any cause.

    Measured: From the date of randomization to the date of death from any cause, assessed up to 3 years

  2. Progression-free survival (PFS)

    PFS in both arms; defined as the time from randomization to the date of the first documented PD determined by the Investigator assessment by RECIST 1.1 or death due to any cause, whichever occurs first

    Measured: From randomization to the date of the first documented disease progression or death due to any cause, up to 3 years

  3. Best overall response (BOR)

    BOR according to Response Evaluation Criteria Solid Tumors (RECIST) v1.1 in both arms; defined as the best response designation (CR, PR, SD or PD), evaluated on all radiological evaluations available and related to study treatment period.

    Measured: From randomization to the date of progression, death or subsequent anti-cancer therapy, up to 3 years

  4. Disease control rate (DCR)

    DCR in both arms according to RECIST v1.1; defined as at least a CR, PR or SD radiological evaluation designation on all radiological evaluations available and related to study treatment period.

    Measured: Up to achievement of best overall response (BOR) of CR or PR or SD, up to 3 years

  5. Incidence and grade of adverse events (AEs) and serious adverse events (SAEs) [Safety and tolerability]

    Incidence and grade of AEs and SAEs, according to NCI-CTCAE v 5.0 in both arms

    Measured: Assessed 28 days after the last administration of treatment or after the end of the treatment visit

  6. Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration

    ECOG PS deterioration is defined as the first increase of at least one point from baseline. The ECOG PS scale ranges from 0 (fully active, asymptomatic) to 4 (completely bedridden), with higher scores indicating worse functional status and poorer prognosis.

    Measured: Time from baseline up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2025
  2. Study startSep 2025 (estimated)
  3. Primary completionDec 2028 (estimated)
  4. Study completionDec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is prospective, multicenter, comparative randomized phase II study design to assess the impact of a biweekly administration (experimental Arm A) compared to a conventional administration (control Arm B) on the rate of grade 3-4 neutropenia in metastatic colorectal cancer (mCRC) patients treated with trifluridine/tipiracil plus bevacizumab.
Masking
None (open label)
Enrolment
162 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07071844
Sponsor's protocol ID
BETWEEN
Acronym
BETWEEN
Status last verified
Jul 2025
First submitted
19 Jun 2025
Last updated
17 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trifluridine/tipiracil and Bevacizumab in people with Metastatic Colorectal Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 10 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Marie-Line GARCIA LARNICOL, MD (+33 (01) 40 29 85 04, marie-line.garcia-larnicol@gercor.com.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The occurrence of at least one grade 3-4 neutropenia (time frame: From randomization up to 14 days after the end of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07071844.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.

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